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C1q is a molecular switch dictating the monocyte to dendritic cell (DC) transition and arrests DCs in an immature phenotype
Author(s) -
Hosszu Kinga K,
SantiagoSchwarz Frances,
Peerschke Ellinor I,
Ghebrehiwet Berhane
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.673.1
Subject(s) - microbiology and biotechnology , cd14 , dendritic cell , monocyte , immune system , biology , cd11c , cd86 , phenotype , immunology , t cell , gene , biochemistry
Complement protein C1q plays a crucial role in regulating peripheral tolerance by facilitating clearance of apoptotic debris and modulating T cell proliferation. Moreover, C1q is emerging as a moderator of dendritic cell (DC) activity. Immature DCs (iDC) are able to secrete C1q. We postulated that such locally secreted C1q regulates the transition from monocytes to DCs. Using flow cytometric analysis we show here that monocyte‐derived DCs cultured in the presence of soluble C1q failed to down regulate CD14 and expressed reduced levels of CD83, DR and CD86. The inhibition of DC maturation was not due to apoptosis, as assessed by lack of annexin V binding and morphological examination. Instead, multiparametric analysis revealed the development of CD14+CD11c+CD16+/− cells representing a subset of iDCs. Monocyte‐DC precursors from the outset expressed gC1qR, the receptor for globular heads of C1q. In contrast, cC1qR, the receptor for the collagen tails of C1q, was lacking on these cells despite the expression of its partner CD91, indicating that inhibition of DC growth by C1q occurs via C1q‐gC1qR interactions. Significantly, pathogens such as hepatitis C virus, which bind gC1qR, may exploit this system by mimicking C1q to escape the acquired immune response. We propose that C1q operates at a critical checkpoint during the monocyte to DC transition and helps maintain immune tolerance by signaling via gC1qR. [Supported by NIH Grant R01 AI‐060866 (to BG) and R03 AR‐05396 (to FSS)]